This project is to study the effect of biological response modifier thymosin on the production of interferon, which is also a biological response modifier. The specific aims of the proposed study are to answer the following questions: (1)\Do thymosins qualitatively or quantitatively modulate serum interferon production? (2)\Does thymosin treatment affect the production of IFN-gamma by spleen cells induced by Con A or other inducers? (3)\What is the target cell population for each thymosin polypeptide in its modulation of interferon production? (4)\Is the modulation of interferon production the result of regulation by thymosin polypeptides of the number of interferon-producing cells or is it an alteration in the amount of interferon per cell? (5)\Do thymosins alter hyporesponsiveness to interferon induction? Seven-week-old C57B1/6 mice will be treated with the optimum regimens of one of the thymosin polypeptides (alpha1, alpha7, beta3, beta4) to be developed in the initial phase of the study. Animals will be induced with a viral inducer and serum interferon level determined or the spleen removed for evaluation of responsiveness to Con A or staphylococcus enterotoxin A. Spleen cells from thymosin-treated animals will be separated to determine the target polypeptide for each thymic hormone. The number of splenic interferon-producing cells of treated and untreated animals will be determined and their productivity evaluated by the modified method of Ito, et al. Finally, the established method of evaluation of hyporesponsiveness to interferon induction in intact animals and in splenic cell culture will be used to study the effect of thymosin treatment. Optimal doses of either thymosin Fr.5 (200 micrograms) or alpha1 (5 micrograms) given 12 hours before the IFN inducer enhances IFN production. In contrast, preliminary experiments suggest that beta4 does not alter production of IFN.